Biotech Values

[urche]

Re: GERN telomerase vaccine in prostate cancer

It is interesting to compare the GERN PR spin vs the actual abstract in Journal of Immunology (http://tinyurl.com/3w8q6).

Unfortunately, the full article is not available without a subscription. Here is the abstract:

Telomerase reverse transcriptase (hTERT) represents an attractive target for cancer immunotherapy because hTERT is reactivated in most human tumors. A clinical trial was initiated in which hTERT mRNA-transfected dendritic cells (DC) were administered to 20 patients with metastatic prostate cancer. Nine of these subjects received DC transfected with mRNA encoding a chimeric lysosome-associated membrane protein-1 (LAMP) hTERT protein, allowing for concomitant induction of hTERT-specific CD8+ and CD4+ T cell responses. Treatment was well tolerated. Intense infiltrates of hTERT-specific T cells were noted at intradermal injection sites after repeated vaccination. In 19 of 20 subjects, expansion of hTERT-specific CD8+ T cells was measured in the peripheral blood of study subjects, with 0.9–1.8% of CD8+ T cells exhibiting Ag specificity. Patients immunized with the chimeric LAMP hTERT vaccine developed significantly higher frequencies of hTERT-specific CD4+ T cells than subjects receiving DC transfected with the unmodified hTERT template. Moreover, CTL-mediated killing of hTERT targets was enhanced in the LAMP hTERT group, suggesting that an improved CD4+ response could augment a CTL response. Vaccination was further associated with a reduction of prostate-specific Ag velocity and molecular clearance of circulating micrometastases. Our findings provide a rationale for further development of hTERT-transfected DC vaccines in the treatment of prostate and other cancers.





A couple of points come to my mind:
1)The GERN vaccine is not specific to prostate cancer. Rather, it appears to be a general immune stimulant using Telomerase reverse transcriptase (hTERT) as antigen. The fact that it appears to be active against prostate cancer is suggestive that it will have similar effect in numerous other malignancies. Unfortunately, that also implies to me that its effect will not be specific enough to avoid significant side-effects.
2) The conclusion of the authors, if anything, seems to independently validate or at least support Provenge (also a dendritic cell vaccine). Maybe the connection between the two vaccines is too indirect to make that connection. But, I see see this as more validation than a threat to Provenge.
3) If anyone has access to the full article, I'd like to see the methods to learn how they came up with increase in PSA doubling time to 100 months. Something sounds wrong with that data.
4) If this vaccine can increase PSA doubling time and Provenge can increase survival, then there could be a compelling reason to use them together.
5) This abstract reminds me of what has always made me nervous about Provenge---the fact that the vaccine is based on PAP, not a very specific and far from ideal prostate cancer antigen.

I think I've already said way too much about a phase 1-2 study abstract.